Cited by 323Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromatin Remodeling and Cancer

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The KAP1 Corepressor Functions To Coordinate the Assembly of De Novo HP1-Demarcated Microenvironments of Heterochromatin Required for KRAB Zinc Finger Protein-Mediated Transcriptional Repression

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Sripathy, Smitha P., Stevens, Jessica, Schultz, David C.·2006·Molecular and Cellular Biology

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Abstract

KAP1/TIF1beta is proposed to be a universal corepressor protein for the KRAB zinc finger protein (KRAB-zfp) superfamily of transcriptional repressors. To characterize the role of KAP1 and KAP1-interacting proteins in transcriptional repression, we investigated the regulation of stably integrated reporter transgenes by hormone-responsive KRAB and KAP1 repressor proteins. Here, we demonstrate that depletion of endogenous KAP1 levels by small interfering RNA (siRNA) significantly inhibited KRAB-mediated transcriptional repression of a chromatin template. Similarly, reduction in cellular levels of HP1alpha/beta/gamma and SETDB1 by siRNA attenuated KRAB-KAP1 repression. We also found that direct tethering of KAP1 to DNA was sufficient to repress transcription of an integrated transgene. This activity is absolutely dependent upon the interaction of KAP1 with HP1 and on an intact PHD finger and bromodomain of KAP1, suggesting that these domains function cooperatively in transcriptional corepression. The achievement of the repressed state by wild-type KAP1 involves decreased recruitment of RNA polymerase II, reduced levels of histone H3 K9 acetylation and H3K4 methylation, an increase in histone occupancy, enrichment of trimethyl histone H3K9, H3K36, and histone H4K20, and HP1 deposition at proximal regulatory sequences of the transgene. A KAP1 protein containing a mutation of the HP1 binding domain failed to induce any change in the histone modifications associated with DNA sequence…

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KRAB-zinc finger protein gene expansion in response to active retrotransposons in the murine lineage
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Phosphorylation of TRIM28 Enhances the Expression of IFN-β and Proinflammatory Cytokines During HPAIV Infection of Human Lung Epithelial Cells
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Genome and epigenome engineering CRISPR toolkit for in vivo modulation of cis-regulatory interactions and gene expression in the chicken embryo
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Epigenetic Gene Silencing by the SRY Protein Is Mediated by a KRAB-O Protein That Recruits the KAP1 Co-repressor Machinery*
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BackgroundMethodInfluential
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Primer Binding Site-Dependent Restriction of Murine Leukemia Virus Requires HP1 Binding by TRIM28
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Recombinant covalently closed circular DNA of hepatitis B virus induces long‐term viral persistence with chronic hepatitis in a mouse model
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“transferable module with DNA binding–dependent transcriptional repression activity.((23,24)) The KRABCre fusion protein induced rcccDNA with an efficiency similar to wt Cre (Fig.”
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Emerging role of SETDB1 as a therapeutic target
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Sumoylation of the Transcriptional Intermediary Factor 1β (TIF1β), the Co-repressor of the KRAB Multifinger Proteins, Is Required for Its Transcriptional Activity and Is Modulated by the KRAB Domain
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“The RBCC domain is followed by a ~200 amino acid intrinsically disordered region (IDR) (Figures 2A, B) that contains an internal PxVxL motif involved in HP1-binding for gene repression (Ryan et al., 1999; Sripathy et al., 2006), and a C-terminal tandem plant homologybromodomain (PHD-BD) cassette involved in intramolec…”
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SUMOylation of the Transcriptional Co-Repressor KAP1 Is Regulated by the Serine and Threonine Phosphatase PP1
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Histone H3 lysine methylation in cognition and intellectual disability disordersPreprint
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“These TFs contain a transcriptional repression domain KRAB (Krüppel-associated box) and thereby can bind the corepressor KRAB-associated protein 1 (KAP1) which, in turn, may recruit the H3K9 KMT SETD1B to the locus (Sripathy et al. 2006).”
Background

Authors: Sripathy, S. P., Stevens, J., & Schultz, D. C.
Affiliations: Case Comprehensive Cancer Center (US)
ORCID: Sripathy, Smitha P.
Schultz, David C.
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2006-11-01
Volume: 26
Issue: 22
Pages: 8623-8638
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.00487-06
PMC: PMC1636786
OpenAlex: W2105073128
Cited by: 323
References: 70
Citations by year: 2026: 9 · 2025: 10 · 2024: 20 · 2023: 15 · 2022: 14 · 2021: 21 · 2020: 24 · 2019: 14 · 2018: 14 · 2017: 14 · 2016: 15 · 2015: 19 · 2014: 13 · 2013: 12 · 2012: 20
FWCI: 6.11
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Case Comprehensive Cancer Center, Case Western Reserve University
National Cancer Institute (K01CA099093, CA-99093)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: KRAB zinc finger proteins, transcriptional repression, heterochromatin, HP1 proteins, SETDB1, PHD finger, bromodomain, histone modifications, H3K9 trimethylation, H3K4 methylation, nuclear compartmentalization, chromatin templates, RNA polymerase II recruitment
MeSH terms: Tripartite Motif-Containing Protein 28, Chromobox Protein Homolog 5, Cell Line, Chromatin, DNA-Binding Proteins, Heterochromatin, Histones, Hormones, Humans, Histone-Lysine N-Methyltransferase, Protein Methyltransferases, Repressor Proteins, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Transfection, Genes, Reporter, Integrases, Saccharomyces cerevisiae Proteins, RNA, Small Interfering

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The KAP1 Corepressor Functions To Coordinate the Assembly of De Novo HP1-Demarcated Microenvironments of Heterochromatin Required for KRAB Zinc Finger Protein-Mediated Transcriptional Repression

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